1. Field of the Invention
This invention relates to the treatment of ocular inflammation such as uveitis. More particularly, this invention relates to pharmaceutical compositions comprising a nitrone compound and methods for treating ocular inflammation using such compositions.
2. State of the Art
Uveitis is an inflammation of the uvea, the middle layer of tissue behind the white of the eye. This condition is sight-threatening and causes about 10 percent of the blindness in the United States. The cause of uveitis is poorly understood, but a variety of systemic diseases are associated with it. In at least one form of uveitis, free radicals have been demonstrated to be part of the disease process.
Corticosteroids, such as dexamethasone, are currently used to treat uveitis. However, the prolonged use of corticosteroids to treat such inflammation is associated with ocular hypertension and/or glaucoma. Accordingly, a need exists for novel pharmaceutical compositions which safely and effectively treat ocular inflammation conditions, such as uveitis. It has now been discovered that certain nitrones compounds are useful for treating ocular inflammation, especially inflammation of the outer and middle eye, such as uveitis. The nitrone compounds useful for this purpose include, for example, .alpha.-(phenyl)-N-tert-butylnitrone (PBN), 5,5-dimethylpyrroline-N-oxide (DMPO) and .alpha.-(4-pyridyl 1-oxide)-N-tert-butyl nitrone (POBN) and derivatives thereof.
Nitrone compounds have been previously reported to be useful as therapeutics. See, for example, U.S. Pat. Nos. 5,025,032; 5,036,097; 5,527,828; 5,532,277 and 5,445,272; and published PCT Patent Application Nos. WO 91/05552 and WO 92/22290. Nitrone compounds, such as PBN, have also been used as analytical reagents for detecting highly reactive free radicals using electron spin resonance (ESR). See, for example, Bull. Chem. Soc. Jpn., 1994, 67, 165; Appl. Magn. Reson., 1992, 3, 1021; and Aldrichimica Acta, 1979, 12, 23.